Stephen T. Bartlett

Comparison of open and laparoscopic live donor nephrectomy

OBJECTIVE This study compares an initial group of patients undergoing laparoscopic live donor nephrectomy to a group of patients undergoing open donor nephrectomy to assess the efficacy, morbidity, and patient recovery after the laparoscopic technique. SUMMARY BACKGROUND DATA Recent data have shown the technical feasibility of harvesting live renal allografts using a laparoscopic approach. However, comparison of donor recovery, morbidity, and short-term graft function to open donor nephrectomy has not been performed previously. METHODS An initial series of patients undergoing laparoscopic live donor nephrectomy were compared to historic control subjects undergoing open donor nephrectomy. The groups were matched for age, gender, race, and comorbidity. Graft function, intraoperative variables, and clinical outcome of the two groups were compared. RESULTS Laparoscopic donor nephrectomy was attempted in 70 patients and completed successfully in 94% of cases. Graft survival was 97% versus 98% (p = 0.6191), and immediate graft function occurred in 97% versus 100% in the laparoscopic and open groups, respectively (p = 0.4961). Blood loss, length of stay, parenteral narcotic requirements, resumption of diet, and return to normal activity were significantly less in the laparoscopic group. Mean warm ischemia time was 3 minutes after laparoscopic harvest. Morbidity was 14% in the laparoscopic group and 35% in the open group. There was no mortality in either group. CONCLUSIONS Laparoscopic live donor nephrectomy can be performed with morbidity and mortality comparable to open donor nephrectomy, with substantial improvements in patient recovery after the laparoscopic approach. Initial graft survival and function rates are equal to those of open donor nephrectomy, but longer follow-up is necessary to confirm these observations.

Clinical Course of Polyoma Virus Nephropathy in 67 Renal Transplant Patients

Polyoma virus (PV) can cause interstitial nephritis and lead to graft failure in renal transplant recipients. The clinical course of patients with polyoma virus nephritis (PVN) is not well understood, partially due to its relatively low incidence. This study is a retrospective analysis of our experience over 4 yr. The specific purpose is to outline the clinical course and outcome of patients with PVN and to study the relationship between immunosuppression and the disease process. Between June 1997 and March 2001, 67 patients with graft dysfunction were found to have biopsy-proven PVN. The diagnosis was made at a mean of 12.8 +/- 9.9 mo posttransplantation. The majority of patients were men (79%) with a mean age of 54 +/- 14 yr (range, 28 to 75). All patients received immunosuppression with a calcineurin inhibitor (tacrolimus in 89% of patients). All patients except two received mycophenolate mofetil and prednisone. After the diagnosis of PVN, maintenance immunosuppression was reduced in 52 patients and remained unchanged in 15 patients. After reduction of immunosuppression, eight patients (15.3%) developed acute rejection and six (11.5%) became negative for PV in biopsy and urine. After a mean observation period of 12.6 mo (mean of 26 mo posttransplantation), 16.4% of patients had lost their grafts (8 of 52 in the reduction group and 3 of 15 in the no change group). In comparison to a case-matched polyoma virus-negative control group, the PVN patients were older (P =.0004) and there was a predominance of men (P = 0.02). Kaplan-Meier analysis demonstrated that patients with PVN had reduced graft survival compared with negative controls (P =.0004). It is concluded that PVN is a serious hazard for renal transplant recipients and contributes directly to graft loss. Antiviral drugs are needed, as the reduction of immunosuppression alone may not significantly improve graft function in patients with already established PVN. Although multiple factors probably play a role in the development of PVN, judicious use of immunosuppressive agents is indicated to minimize the occurrence of this infection.

Morbidity and mortality after living kidney donation, 1999-2001: Survey of United States transplant centers

There have been two recent trends in living kidney donation: increased acceptance of living donors and increased acceptance of laparoscopic nephrectomy (LN).

Increased Rates of Donation With Laparoscopic Donor Nephrectomy

ObjectiveTo examine the impact of laparoscopic nephrectomy and recipient education on the proportion of kidney recipients who could identify a potential live donor, and on the live donor (LD) transplantation rate. Summary Background DataLaparoscopic donor nephrectomy (LDN) results in less postoperative surgical pain, a shorter hospital stay, and quicker recovery than the standard open donor nephrectomy (ODN). The authors hypothesized that the availability of this less invasive surgical technique would enhance the willingness of family and friends to donate. MethodsThe study population consisted of 3,298 end-stage renal disease patients referred for kidney transplant evaluation between November 1991 and February 2000, divided into three groups. The first group received no formal LD education and had only ODN available. The second group received formal education about the LD process and had only ODN available. The third group had both formal LD education and LDN available. Records were examined to determine what proportion of each group had any potential donors tissue-typed, and the rate at which they received an LD transplant. ResultsBefore LDN availability and formal LD education, only 35.1% of referrals found a potential donor, and only 12.2% received an LD transplant within 3 years. Institution of a formal education program increased the volunteer rate to 39.0%, and 16.5% received an LD transplant. When LDN became available, 50% of patients were able to find at least one potential donor, and within 3 years 24.7% received an LD transplant. Regression analysis indicated that availability of LDN was independently associated with a 1.9 relative risk of receiving an LD transplant. Kaplan-Meier death-censored 1- and 3-year graft survival rates for ODN transplants were 95.8% and 90.6%, versus 97.5% and 94.8% for LDN. ConclusionsThe availability of LDN and an LD family education program has doubled the live donor transplantation rate, and outcomes remain excellent.

A comparison of recipient renal outcomes with laparoscopic versus open live donor nephrectomy.

Background. Laparoscopic donor nephrectomy (laparoNx) has the potential to increase living kidney donation rates by reducing the pain and suffering of the donor. However, renal function outcomes of a large series of recipients of laparoNx have not been studied. Methods. We retrospectively reviewed the records of 132 recipients of laparoNx done at our center between 3/96 and 11/97 and compared them to 99 recipients of kidneys procured by the open technique (openNx) done between 10/93 and 3/96. Results. Significantly more patients in the laparoNx group (25.2%) were taking tacrolimus within the first month than those in the openNx group (2.1%). Mean serum creatinine was higher in laparoNx compared with openNx at 1 week (2.860.3 and 1.860.2 mg/dl, respectively; P50.005) and at 1 month (2.060.1 and 1.660.1 mg/dl, P50.05) after transplant. However, by 3 and 6 months, the mean serum creatinine was similar in the two groups (1.760.1 versus 1.560.05 mg/dl, and 1.760.1 versus 1.760.1, respectively). By 1 year posttransplant, the mean serum creatinine for laparoNx was actually less than that for openNx (1.460.1 and 1.760.1 mg/dl, P50.03). Although patients in the laparoNx compared to the openNx group were more likely to have delayed graft function (7.6 versus 2.0%) and ureteral complications (4.5 versus 1.0%), the rate of other complications, as well as hospital length of stay, patient and graft survival rates were similar in the two groups. Conclusion. Although laparoNx allografts have slower initial function compared with openNx, there was no significant difference in longer term renal function. Kidney transplantation is considered to be the treatment of choice for end-stage renal failure. Insufficient supply of organs for donation has produced long waiting times for many patients who may benefit from transplantation (1). During this period patients accumulate the morbidity of renal failure, they must endure the lifestyle limitations of dialysis, and they often die while waiting for the organ sharing system to grant them this resource. Live donor renal transplantation represents a large potential supply of organs that may relieve much of this shortage. Additionally, recipients of live renal transplants may reap benefits of improved patient and allograft survival that have been clearly demonstrated in this population (2,3). Although unilateral nephrectomy has proven to be safe and the solitary kidney state has been found to be well tolerated in a carefully chosen candidate for donation (4,5), substantial disincentives to donation exist. These include a significant hospitalization, prolonged convalescence period with time away from jobs, intractable perioperative pain, and, for some, cosmetic concerns of the resulting

Human polyoma virus in renal allograft biopsies: Morphological findings and correlation with urine cytology

Human polyoma virus (PV) interstitial nephritis occurs in immunosuppressed patients after reactivation of latent virus in renal epithelium. Currently, there is neither general consensus about the incidence of clinically significant PV infection in renal transplants nor conclusive evidence determining its significance in the long-term graft outcome. We evaluated 601 renal transplant biopsy specimens (from 365 patients) by routine light microscopy and immunoperoxidase stains with antibody against SV40 (which cross reacts with PV). We also examined urine samples from 200 patients (100 obtained concurrently with a renal biopsy in patients presenting with acute graft dysfunction and 100 from patients with stable graft function). Electron microscopic evaluation was performed in 50 renal biopsy specimens and in 23% of all urine samples. PV was identified in 1.8% biopsy specimens (1.9% of patients). PV interstitial nephritis showed the typical viral cytopathic changes in tubular epithelial cells associated with marked tubular damage and a disproportionately mild degree of tubulitis. There was no difference in the incidence of PV in the urine of patients with acutely deteriorating versus stable renal function (18% and 19%, respectively); however, urines with large numbers of infected cells (> 10/cytospin) and inflammatory changes in the sediments corresponded invariably to patients with acute allograft dysfunction (8 of 8), and in most cases to biopsy specimens showing PV interstitial nephritis (7 of 8). Based on these findings, urine samples seem to be the most sensitive and cost-effective screening method for PV infection; only urine samples with inflamed sediments and abundant infected cells correlate with clinically significant disease. In these cases, examination of a renal biopsy is indicated. Immunohistochemical stains are useful to confirm the presence of PV but do not increase the sensitivity of diagnosis of PV if this is not already suspected on routine light microscopy. In our material, immunostains were helpful ruling out the presence of PV in a small number of biopsy specimens (2%) that showed markedly reactive tubular cells resembling PV infection. Most patients with PV interstitial nephritis responded to decreased immunosuppression; however, the decay in graft function (based on creatinine slopes) was significantly more rapid in these patients than in matched controls. Evidence of PV infection should be systematically sought in renal biopsy specimens and urine samples from renal allograft recipients.

Continuous intravenous infusion of epoprostenol for the treatment of portopulmonary hypertension.

The association of pulmonary hypertension with portal hypertension, also called portopulmonary hypertension (PPHTN), is a known complication of chronic liver disease. Previously, the presence of PPHTN was considered to be a contraindication to orthotopic liver transplantation (OLT). Although there are selected case reports of successful OLT in the setting of PPHTN, an excessive mortality rate is associated with OLT and PPHTN. Heretofore, therapy for chronic management of PPHTN was lacking. Recently, continuous intravenous infusion of epoprostenol has been demonstrated to improve symptomatology and survival in the general population of patients with primary pulmonary hypertension. We now report the use of epoprostenol in the more specific instance of PPHTN. Over a period of 6-14 months, epoprostenol (10-28 ng/kg/min) therapy was associated with a 29-46% decrease in mean pulmonary artery pressure, a 22-71% decrease in pulmonary vascular resistance, and a 25-75% increase in cardiac output in a group of four patients. These results suggest that effective chronic therapy for PPHTN is available. In conjunction with inhaled nitric oxide as acute intraoperative therapy, epoprostenol infusion represents an additional therapeutic option for treatment of PPHTN in the liver transplant candidate.

Laparoscopic versus open donor nephrectomy: comparing ureteral complications in the recipients and improving the laparoscopic technique.

BACKGROUND Laparoscopic live donor nephrectomy (LDN) is a recently developed procedure, the performance of which needs to be studied. Given the reported advantages in the donors, this study looks at graft outcome and ureteral complications in recipients of kidneys procured by open donor nephrectomy (ODN) versus LDN. METHODS The LDN recipients consisted of 193 patients since 3/27/96. A total of 168 ODN recipients from 1991 to 1998 served as controls. Immunosuppression protocols were similar for both groups. RESULTS Two-year graft survival for LDN and ODN was 98% and 96%, respectively. Two-year patient survival for LDN and ODN was 98% and 97%, respectively. The incidence of delayed graft function and mean serum creatinine at 3 and 12 months was similar in both groups. However, the number of ureteral complications that required operative repair was significantly higher for LDN recipients compared to ODN recipients, 7.7% (n=15) vs. 0.6% (n=1) respectively (P=0.03). Ureteral stenting was required in an additional 3.1% (n=6) of LDN and 2.4% (n=4) of ODN (P=NS). There was, however, a learning curve with time. For the first 130 LDN patients, a total of 20 ureteral complications were recorded, whereas only one occurred in the more recent 63 patients (P=0.03). CONCLUSIONS The higher ureteral complication rate in LDN recipients has improved over time as technical causes have been identified. We have noted significant improvement in ureteral viability by using the endogastrointestinal anastomosis instrument on the ureter and peri-ureteral tissue. LDN is therefore an excellent alternative to ODN. Identification of hazards unique to this technique is critical before its broader application.

A novel approach to the treatment of chronic allograft nephropathy

BACKGROUND Progressive deterioration of renal function in kidney transplant recipients is the leading cause of graft failure. Both nonimmunologic and immunologic mechanisms contribute to this deterioration. METHODS Twenty-eight cyclosporine (CsA)-treated renal transplant recipients (21 cadaveric, 5 living, 2 simultaneous kidney-pancreas) with progressive deterioration of renal function were prospectively enrolled in a clinical trial and had their immunosuppressive regimen changed 24.3+/-7.7 months after transplant. All patients had their CsA dose reduced by 50%, azathioprine was discontinued, and mycophenolate mofetil was added to the medical regimen. The mean creatinine of the patients at the initiation of the change in immunosuppression was 3.5+/-1.2 mg/dl (range 1.9 to 6.2 mg/dl). RESULTS Before the change in immunosuppression, the mean loss in renal function as indicated by the least-squares slope of the reciprocal of creatinine versus time was -0.006+/-0.002 (mg/dl)-1 per month. The change in immunosuppression significantly decreased the rate of loss in renal function for most patients when compared with their pretreatment values with a mean slope of 0.007+/-0.003 (mg/dl)-1 per month (P=0.003). Renal function improved in 21 of 28 patients. Only one patient had continued deterioration of renal function. In a multivariate analysis adjusting for CsA dose, mean arterial blood pressure, and baseline creatinine, the change in immunosuppression was significantly associated with improved renal function (P=0.02). There were no acute rejections after the immunosuppression change. CONCLUSIONS We conclude that adding mycophenolate mofetil and reducing CsA in patients with chronic deterioration of graft function is well tolerated and results in a short-term improvement in renal function.

A high panel-reactive antibody rescue protocol for cross-match-positive live donor kidney transplants.

Background. Alloimmunization can present a virtually insurmountable barrier to kidney transplantation. Past protocols to desensitize patients using plasmapheresis and cyclophosphamide have not been broadly applied because of the fear of complications, including high rates of immunologic failure. Methods. Fifteen patients with a positive donor-recipient cross-match were desensitized with plasmapheresis to permit live donor (LD) transplantation under newer maintenance immunosuppressants. Pretransplant the patients received plasmapheresis three times weekly for a planned maximum of six treatments, plus intravenous hyperimmune globulin, tacrolimus, mycophenolate mofetil, and prednisone. Patients who were successfully desensitized and received transplants were given 10 days of OKT3 postoperatively. Results. Eleven of the 15 patients became anti-human globulin cross-match-negative after one to five plasmapheresis treatments and underwent LD transplantation. Relatively low initial titers of donor-specific antibody were predictive of successful attainment of a negative cross-match. Few side effects and rejection episodes were observed. All transplant patients remain dialysis-free after 3–26 months of follow-up. Conclusion. A positive cross-match is not necessarily a contraindication to LD transplantation, especially for patients with low donor-specific alloantibody titers.